Institute of General Microbiology, Kiel University, Kiel, Germany.
Research group Stochastic Evolutionary Dynamics, Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
PLoS Genet. 2023 Aug 3;19(8):e1010829. doi: 10.1371/journal.pgen.1010829. eCollection 2023 Aug.
The emergence of antibiotic resistance under treatment depends on the availability of resistance alleles and their establishment in the population. Novel resistance alleles are encoded either in chromosomal or extrachromosomal genetic elements; both types may be present in multiple copies within the cell. However, the effect of polyploidy on the emergence of antibiotic resistance remains understudied. Here we show that the establishment of resistance alleles in microbial populations depends on the ploidy level. Evolving bacterial populations under selection for antibiotic resistance, we demonstrate that resistance alleles in polyploid elements are lost frequently in comparison to alleles in monoploid elements due to segregational drift. Integrating the experiments with a mathematical model, we find a remarkable agreement between the theoretical and empirical results, confirming our understanding of the allele segregation process. Using the mathematical model, we further show that the effect of polyploidy on the establishment probability of beneficial alleles is strongest for low replicon copy numbers and plateaus for high replicon copy numbers. Our results suggest that the distribution of fitness effects for mutations that are eventually fixed in a population depends on the replicon ploidy level. Our study indicates that the emergence of antibiotic resistance in bacterial pathogens depends on the pathogen ploidy level.
在治疗过程中抗生素耐药性的出现取决于耐药等位基因的存在及其在人群中的建立。新的耐药等位基因要么编码在染色体或染色体外遗传元件中；这两种类型都可能在细胞内以多个拷贝存在。然而，多倍体对抗生素耐药性出现的影响仍研究不足。在这里，我们表明抗生素耐药性在微生物种群中的建立取决于倍性水平。在选择抗生素耐药性的进化细菌种群中，我们证明与单倍体元件中的等位基因相比，多倍体元件中的耐药等位基因由于分离漂变而经常丢失。将实验与数学模型相结合，我们发现理论和经验结果之间存在显著的一致性，证实了我们对等位基因分离过程的理解。使用数学模型，我们进一步表明，多倍体对有利等位基因建立概率的影响在低复制子拷贝数时最强，并在高复制子拷贝数时趋于平稳。我们的结果表明，最终在群体中固定的突变的适合度效应分布取决于复制子的倍性水平。我们的研究表明，细菌病原体中抗生素耐药性的出现取决于病原体的倍性水平。
